The specific interactions taking place between Rathke's pouch epithelium and mesenchyme in establishing the vasculature of the anterior pituitary are not known. Causative factors governing cytodifferentiation of cell types of the anterior pituitary are also only poorly understood. Our studies are concerned with characterizing specific aspects of the tissue interactions that function as determinants of pituitary cytodifferentiation and its vasculature. Additional studies are directed at the immunolocalization of estrogen receptor during normal ontogeny through puberty. The results of these experiments will elucidate fundamental tissue interactions governing development of the pituitary vasculature and cytodifferentiation, and also will have relevance for our understanding of pituitary tumorigenesis. Throughout our studies we are using two rat strains, the highly estrogen-sensitive Fischer 344, and comparatively estrogen- insensitive Sprague-Dawley rats. We have demonstrated that epithelio-mesenchymal interactions, including the vasculature, are distinctly different in these rat strains, a circumstance that very likely underlies the tumor susceptibility of F344 rats. Our experiments will determine: 1. The nature of specific interactions taking place between Rathke's pouch epithelium and its mesenchyme during normal ontogeny through puberty. We will especially follow the development of folliculo-stellate (FS) cells and correlate their development with modifications of specific components of the extracellular matrix and the distribution of fibroblast growth factor. 2. The ontogeny of estrogen receptors from fetal stages through puberty, and in estrogen-treated adults. 3. Whether the estrogen-dependency of mammotroph cytodifferentiation inhibited by alpha fetoprotein. 4. Whether kidney capsule grafts of pure FS cells from F344 and 5-D rats will themselves reveal strain specific responses to estrogen. Methods used in our studies are light- and electron microscopy, immunocytochemistry and cryo-immunocytochemistry, and radioimmunoassay.